This invention relates to new and useful benzothiazine dioxide derivatives. More particularly, it is concerned with certain novel 2-acetoxybenzoyl and ring-substituted .alpha.-arylpropionyl derivatives of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide and several other closely-related oxicams, which are of especial value in view of their unique chemotherapeutic properties.
In the past, various attempts have been made to obtain new and better anti-inflammatory agents. For the most part, these efforts have involved the synthesis and testing of various steroidal compounds such as the corticosteroids or non-steroidal substances of an acidic nature such as phenylbutazone, indomethacin and the like, including a new agent known as piroxicam. The latter substance is a member of a class of anti-inflammatory/analgesic N-heteroaryl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides (known as oxicams) described and claimed in U.S. Pat. No. 3,591,584 and is specifically, 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. Other agents of this type are disclosed in U.S. Pat. Nos. 3,787,324, 3,822,258, 4,180,662 and 4,376,768. In U.S. Pat. No. 4,434,164, there are specifically described and claimed the ethylenediamine, monoethanolamine and diethanolamine salts of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, which are particularly valuable in pharmaceutical dosage forms as non-steroidal therapeutic agents for the treatment of painful inflammatory conditions, such as those caused by rheumatoid arthritis, since they are all crystalline, non-hygroscopic, rapidly-dissolving solids with high water solubility. In U.S. Pat. No. 4,309,427, there are disclosed certain novel acyl derivatives of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamine 1,1-dioxide and 4-hydroxy-2-methyl-N-(6-methyl-2-pyridinyl)-2H-1,2-benzothiazine-3-carboxa mide 1,1-dioxide, which are useful as non-steroidal therapeutic agents for alleviating various inflammatory conditions, including those of the skin, especially when given by the topical route of administration. However, in the continuing search for still more improved anti-inflammatory/analgesic agents, there is a need for anti-arthritic agents that are orally administrable and yet at the same time are less ulcerogenic than the parent oxicam compounds of the prior art.